Ajax were given a boost with the full debut of Oleksandr Zinchenko, who arrived from Arsenal in the last week of January. The Ukrainian was given the nod over Owen Wijndal, while Rayane Bounida kept Oscar Gloukh out of the starting XI again.
Zinchenko's debut in the Johan Cruyff ArenA lasted perhaps historically short after a seemingly light foul from Fortuna's Dimitris Limnios caused the left-back's leg to buckle inside two minutes, forcing interim manager Fred Grim to take Zinchenko off after fewer than six minutes.
Zinchenko was vindicated less than a minute after being taken off when Jorthy Mokio, who replaced the sick Youri Regeer, fired Ajax in front from up close after Kasper Dolberg smartly played a free-kick through to the young midfielder.
Bounida doubled Ajax's lead in the 14th minute, perfectly placing the ball in Luuk Koopmans' left-hand corner for his first Eredivisie goal.
Ajax put up a clinic against Fortuna Sittard, who conceded the 3-0 in the 24th minute thanks to Ajax's top scorer, Mika Godts. The Belgian winger, who assisted Bounida's 2-0, curled the ball in the right corner and thus added an assist to Jorthy Mokio's successful evening.
The goals from Mokio, Bounida and Godts made them the first Belgian trio since 2006/07 to all score in the same game.
However, Fortuna didn't go down without a fight: Limnios found space behind Owen Wijndal and was free to cross the ball into the box, where it was put in Vitezslav Jaros's goal by Ajax centre-half Josip Sutalo.
Dolberg came close to his first league goal in nearly a month, but the Danish striker hit the post with a header from Mika Godts' cross. The Dane was denied a goal after an hour when referee Rob Dieperink spotted a push from Dolberg before the latter headed in a Bounida cross.
It was a typically quiet second half for Ajax, who came close to scoring a fourth with 15 minutes to go as Oscar Gloukh, who replaced Davy Klaassen after an hour, got the ball in front of Fortuna's goal, but no team-mate was there to put it in an empty net.
It nearly got exciting in the Johan Cruyff ArenA when former Ajax striker Kaj Sierhuis had the chance to put the ball in an empty net himself, but the Fortuna striker fired it over the bar as the Sittard outfit had just 10 minutes to go in Amsterdam.
Godts put the game to bed within two minutes of Sierhuis' miss, firing the ball past Koopmans at his near post on an assist from Wout Weghorst.
Weghorst nearly gave Ajax a four-goal lead shortly before half-time, but failed to finish his one-on-one, meaning Ajax had their first win in February after draws against Excelsior and AZ. The record Eredivisie champions temporarily moved up to third ahead of NEC's away game at Sparta Rotterdam on Sunday.